Synthesis of 4-amino substituted and 4-unsubstituted 1,10-phenanthroline-3-carboxylic acid derivatives as potential DNA cleavage reagents

Abstract

The synthesis of several new 4-amino substituted and 4-unsubstituted 1,10-phenanthroline-3-carboxylic acid derivatives are reported. The 4-amino derivatives ( 5,6,7) were prepared from 1,4-dihydro-oxo-1,10-phenanthroline-3-carboxylic acid ( 2) via aromatizadon and 4-chlorination, followed by nucleophilic substitution at C4 by the appropiate alkyl amine. The 4-unsubstituted derivatives ( 10,11,12) were prepared by aromatization and 4-chlorination of ethyl 1,4-dihydro4-oxo,1,10-phenanthroline-3-carboxylate. The substituent at C4 was removed by conversion to the 4-tosyl hydrazide, followed by base-catalysed elimination of the hydrazide group. These phenanthroline derivatives were designed as metal-ion-complex mediated DNA cleavage reagents. In both series the 3-carboxylic acid side chain was coupled to β-alanine to facilitate its conjugation with DNA binding molecules. The syntheses of a series of 1,10-phenanthroline-3-carboxylic acid derivatives are reported. The 4-amino derivatives were prepared via the displacement of the 4-chloro atom can be removed non-reductively by conversion to the 4-tosyl hydrazide, which was then eliminated via a base-catalysed mechanism. These derivatives can be conjugated to potential DNA binding ligands via the 3-carboxy-β-alanine side chain.